- Therapeutics
- Jim Knabb
Chimeric antigen receptors (CARs) are hybrid proteins consisting of an antibody binding fragment fused to protein signaling domains that cause T-cells which express the CAR to become cytotoxic. Once activated, these cytotoxic T-cells can selectively eliminate the cells which they recognize via the antibody binding fragment of the CAR. Thus, by engineering a T-cell to express a CAR that is specific for a certain cell surface protein, it is possible to selectively target those cells for destruction. This promising new therapeutic approach is known as adoptive cell therapy.
CD22 is a cell surface protein expressed on a large number of B-cell lineage hematological cancers, such as leukemia and lymphoma. Several promising therapies are being developed which target CD22, including therapeutic antibodies and immunotoxins. This technology concerns the use of a high affinity antibody binding fragment to CD22 (known as m971), as the targeting moiety of a CAR. The resulting CAR can be used in adoptive cell therapy treatment for cancer.
- Treatment of diseases associated with increased or preferential expression of CD22
- Hematological cancers such as chronic lymphocytic leukemia (CLL), hairy cell leukemia (HCL) and pediatric acute lymphoblastic leukemia (ALL)
- High affinity of the m971 antibody binding fragment increases the likelihood of successful targeting
- Targeted therapy decreases non-specific killing of healthy, essential cells, potentially resulting in fewer non-specific side-effects and healthier patients
- Hematological cancers are susceptible to cytotoxic T-cells for treating because they are present in the bloodstream
- Expression of CD22 only on mature cells avoids stem cell elimination during treatment
Rimas Orentas Ph.D. (NCI), Ira Pastan MD, PHD (NCI), Crystal Mackall M.D. (NCI), Dimiter Dimitrov Ph.D (NCI)
- Clinical
Shah NN et. al. CD4/CD8 T-Cell Selection Affects Chimeric Antigen Receptor (CAR) T-Cell Potency and Toxicity: Updated Results From a Phase I Anti-CD22 CAR T-Cell Trial [PMID 32286905]
- U.S. Provisional: U.S. Provisional Patent Application Number 61/717,960 , Filed 24 Oct 2012
- PCT: PCT Application Number PCT/US2013/060332 , Filed 25 Oct 2018
- Foreign Issued: Australian - Patent Number 2013335180, Issued 25 Oct 2018
- Foreign Issued: Australian - Patent Number 2018204257, Issued 18 Jun 2020
- Foreign Filed: Brazil - Patent Application BR112015009003-6, Filed 22 Apr 2015
- Foreign Filed: Canadian - Patent Application 2889055
- Foreign Issued: Chinese - Patent Number ZL 201380061387.5, Issued 12 Jul 2019
- Foreign Filed: - Patent Application 201910500128.7, Filed 11 Jun 2019
- Foreign Issued: European - Patent Number 2912061, Issued 06 Feb 2019
- Foreign Issued: German - Patent Number 2912061, Issued 06 Feb 2019
- Foreign Issued: Spain - Patent Number 2912061, Issued 06 Feb 2019
- Foreign Issued: France - Patent Number 2912061, Issued 06 Feb 2019
- Foreign Issued: United Kingdom - Patent Number 2912061, Issued 06 Feb 2019
- Foreign Issued: Italy - Patent Number 2912061, Issued 18 Feb 2019
- Foreign Filed: Indian - Patent Application
- Foreign Issued: Japanese - Patent Number 6338252, Issued 18 May 2018
- Foreign Filed: Japanese - Patent Application
- Foreign Issued: Russian - Patent Number 2658485, Filed 21 Jun 2018
- Foreign Filed: Russian - Patent Application
- U.S. Patent Issued: U.S. Patent Number 10,072,078, Issued 11 Sep 2018
- U.S. Patent Issued: U.S. Patent Number 10,703,816, Issued 07 Jul 2020
- U.S. Patent Filed: U.S. Patent Application Number 16/869,792, Filed 08 May 2020
- Foreign Issued: Hong Kong - Patent Number HK1213922, Issued 20 Mar 2020
- E-080-2008 - Human and Improved Murine Monoclonal Antibodies Against CD22
- E-017-2017 - Dual Specific Anti-CD22 Anti-CD19 Bicistronic Chimeric Antigen Receptors (CARs)
- E-161-2018 - Improved CD22 Binders for Effective Immunotherapy Against Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL)
- E-106-2015 - Bivalent, Dual Specific Anti-CD22 Anti-CD19 Chimeric Antigen Receptors (CARs)
- Cancer/Neoplasm